This
bulletin is a supplement to, not a substitute for, professional skills and experience.
Users are advised to consult the supporting evidence for a consideration of all the
implications of a recommendation

The Statements

The
Evidence

2a. The World Health
Organisation criteria for classification/diagnosis of osteoporosis
are as follows:

with osteopenia (a BMD of > 1SD below the
young adult mean but <2.5 SD below this valuei); and

with osteoporosis (a BMD of 2.5 standard
deviations or more below the young adult meani.ii) with or
without pre-existing fragility fractures.

2b. The
Royal College of Physicians agree with the recommendations of the Advisory
Group on Osteoporosis and the NHS Executive letter (EL(96)110) that "Health
Authorities should purchase bone density measurement by means of dual
x-ray adsorptiometry (DXA)" i.

Total hip BMD
appears to be as effective as femoral neck BMD for detecting response to bisphosphonate
treatment in the femur in the setting of a clinical trial or similar
research settingiii.(Health gain notation  1
"beneficial")

Detailed recommendations for the use of biochemical
markers of bone turnover in osteoporosis are availableiv.

i. Anonymous. Osteoporosis.
Clinical Guidelines for Prevention and Treatment. London: Royal
College of Physicians, 1999http://www.doh.gov.uk/osteorep.htm
[accessed 29.11.01]
(Type V evidence  expert opinion based on a systematic review of the
literature)ii. Marshall D, Johnell O, Wedel
H. Meta-analysis of how well measures of bone mineral density predict
occurrence of osteoporotic fractures. British Medical Journal 1996;
312: 1254-1259http://www.bmj.com/cgi/content/
full/312/7041/1254[accessed 29.11.01]
(Type IV evidence - systematic review and meta-analysis of 11 cohort
studies, 90,000 person years and 2000 fractures)iii. Blake GM, Preston NG, Patel
R, Herd JM, Fogelman I. Monitoring skeletal response to treatment: Which
site to measure in the femur? Journal of Clinical Densitometry 2000;
3(2): 149-155(Type IV evidence  comparison
of BMD measurements of 152 postmenopausal women enrolled in a trial of
bisphosphonate therapy. Measurements at 0, 1 and 2 years were compared at
six sites in the hip and spine)iv. Delmas PD, Eastell R, Garnero
P, Seibel MJ, Stepan J, for the Committee of Scientific Advisors of the
International Osteoporosis Foundation. The use of biochemical markers of
bone turnover in osteoporosis. Osteoporosis International 2000; suppl.6:
S2-S17(Type V evidence  expert
opinion based on a review of the literature)

2c. The use of the
T-score requires a comparison of the measurement with measurements in a young
reference population. Although fracture risk varies between
populations there is insufficient knowledge at present to recommend that
local reference ranges be usedi. It is recommended that the
NHANES IIIii database be used as an international reference
until further evidence changes this viewi.

2d. Prior
to the publication of the Royal College of Physicians (RCP) guidelinesi,
the major guidelines were produced by the European Foundation for
Osteoporosis and Bone Disease (EFFO)ii and the National
Osteoporosis Foundation of the USA (NOF) iii. All three
guidelines recommend:

a case-finding strategy, rather than mass
screening, for the diagnosis of osteoporosis.

the measurement of BMD, preferably at the hip,
with defined intervention thresholds.

The RCP and the EFFO take a population wide approach
to diagnosis and have provided a list of indicators for the diagnostic use
of BMD. In contrast, the NOF takes an individual approach so that
assessment thresholds vary from individual to individual based on planned
treatment, risk factors and age.

i. Anonymous. Osteoporosis.
Clinical Guidelines for Prevention and Treatment. London: Royal Chttp://www.doh.gov.uk/osteorep.htm
[accessed 29.11.01]
(Type V evidence  expert opinion based on a systematic review of the
literature)ii. Kanis JA, Delmas P, Buckhardt
P, Cooper C, Torgerson D, on behalf of the European Foundation for
Osteoporosis and Bone Disease. Guidelines for diagnosis and management of
osteoporosis. Osteoporosis International 1997; 7: 390-406(Type V evidence  consensus
guidelines based on an extensive review of the literature)iii. Eddy DM, Johnston CC,
Cummings SR et al. Osteoporosis: Review of the evidence for
prevention, disgnosis and treatment and cost-effectiveness analysis. Osteoporosis
International 1998; 8(suppl.4): S1-S88(Type V evidence  expert
opinion based on an extensive review of the literature)

2e. On
the basis of several cost-estimates, the use of bone densitometry for well
defined clinical indications seem to be justifiable in terms of their cost
utilityi.Bone density measurements are
recommended for the following indications where assessment would
influence managementi:

Cost-utility studies
indicate that the targeting of high-risk populations improves
cost-effectiveness. In populations with a relative risk of 2 and
intervention costs of £500 per year for 5 years, there are savings in
women at the age of 80 years. For intervention costs of approximately
£200 per year, cost-effectiveness can be demonstrated for 60 year olds.

2f.
There
is no scientific basis for recommending bone density measurement in mass
screening, or as an extra component in health check-ups of
asymptomatic individuals, with the aim of preventing fracturesi,ii.(Health gain notation 5 "unlikely
to be beneficial")

2g. In comparison to
BMD measurements by DXA quantitative ultrasound (QUS) for bone
measurement does not use ionising radiation, is cheaper, takes up less
space and is easier to use than densitometry techniquesi.

2h. Ultrasound
measurements can predict the risk of hip
fracture in elderly peoplei,ii,iii.

Two large studies of elderly women found that low calcaneal ultrasonic
variables (BUA and SOS) were able to predict increased hip fracture risk
with similar accuracy to BMD measurement by DXAi,ii.

In one study, the relative risk of hip fracture for one SD reduction was
2.0 (95% CI 1.6-2.4) for ultrasound attenuation and
1.7 (1.4-2.1) for speed of sound, compared with 1.9
(1.6-2.4) for BMDi. In the second study
each one SD reduction in calcaneal BUA was associated with a doubling of
the relative risk for hip fracture (RR=2.0, 95% CI 1.5-2.7);
a similar relationship was observed with bone mineral density of the
calcaneus (RR=2.6, 95% CI 1.9-3.0) and femoral neck
(RR=2.6, 95% CI 1.9-3.8)ii.

Using the results from a portable dry system, Cox regression analysis,
adjusted for age and sex, showed that the relative risk (RR) of hip
fracture for each standard deviation reduction was 2.3 (95%
CI 1.4-3.7) for BUA and 1.6 (95% CI 1.1-2.3)
for SOS. Slightly weaker relationships were found for any fracture.
Multivariate analyses identified low BUA values and immobility as the
strongest predictors for hip fractures and any fractureiii.(Health gain notation  4
"unknown")Caveat: This
was a small, low power study for fracture outcome; Only elderly people
living in homes/sheltered housing were examined; fractures were
self-reported.

2i. Linear regression
coefficients between calcaneal QUS
parameters and DXA were only modest in a group of 25-75 year-old Dutch
women. In a subgroup of premenopausal women correlations between BUA and
BMD at the hip and femoral neck were lower compared to those in
postmenopausal women. The predictive value of QUS parameters for BMD is
limited, therefore it is not appropriate to use QUS as a surrogate for DXAi.

There are significant differences in the classification of osteoporosis/osteopenia
depending on the site measured and the technique used for bone mass
measurement. For example, according to the proposed WHO guidelines, the
percentage of women classified as osteopenic ranged from 25.9% by BUA at
the heel, to 43% by BMD at the femoral neck. For men, the same range is
from 20.5% by BUA to 44.1% by BMD at the femoral neck. For classification
into the osteoporotic group, the range was from 2.5% by intertrochanteric
BMD to 24.4% by BMD at Wards triangle for women and from 0% by SOS to
29.0% by BMD at Wards triangle for men. The development of technique
and site specific cut-off values may increase the accuracy of the
classification of osteoporosis and osteopenia in both men and womenii.

Although DXA and QUS parameters are significantly correlated, QUS
parameters cannot predict osteopenia as defined by DXA, and sensitivities
and specificities of QUS parameters were not sufficiently high for QUS to
be used as an alternative to DXA. Further prospective studies with long
follow-up periods are necessary to validate QUS measurements in subjects
with low, normal or osteopenic valuesiii.Caveat: The
authors accept that QUS is an independent predictor of fracture risk and
suggest, as other authors have suggested, that it measures not just BMD
but other properties such as elasticity and trabecular architecture.

i. Dubois EF, van den
Bergh JP, Smals AG et al. Comparison of quantitative ultrasound
parameters with dual energy X-ray absorptiometry in pre- and
postmenopausal women. Netherlands Journal of Medicine 2001; 58(2):
62-70(Type IV evidence  Comparison
of calcaneal QUS and DXA measurements, at spine, total hip and femoral
neck, of 217 pre- and postmenopausal women (aged 25-75) referred for a BMD
measurement because of osteoporosis in at least one family member either
in the first or in the second degree)

2j. Clinical risk factors
affect calcaneal BUA and SOS Z score measurements to the same extent as
axial BMD Z score measurements. Provided revised diagnostic criteria are
adopted, similar proportions of postmenopausal women are identified as
osteopenic or osteoporotic as with BMDi.(Health gain notation  2 "likely
to be beneficial")Caveats: Calcaneal
QUS appears to be responsive to the effect of antiresorptive therapies but
these are often more pronounced re spinal BMD. The authors note that their
revised criteria may be device specific (Hologic Sahara/Osteometer DTUone)
and would need to be confirmed for other instruments. The reference group
was selected from the study population (of referred and volunteer
subjects) and may not be representative of the whole population.

The WHO threshold of T score = -2.5 for diagnosing osteoporosis requires
modification when using QUS to assess skeletal status. For three QUS
devices, a T-score threshold of 1.80 would result in the same
percentage of postmenopausal women classified as osteoporotic as the WHO
threshold for BMD measurements. Corresponding T-score thresholds for
individual measurement parameters on the two commercially available
ultrasound devices were 1.61, -1.94 and 1.90 for Sahara BUA, SOS and
estimated BMD respectively, and 1.45 and 2.10 for DTU BUA and SOS
respectively. Additional studies are needed to determine suitable
T-score thresholds for other commercial QUS devicesii.

ii. Frost ML, Blake GM, Fogelman I. Can
the WHO criteria for diagnosing osteoporosis be applied to calcaneal
quantitative ultrasound? Osteoporosis International 2000; 11:
321-330(Type IV evidence  comparison
of DXA measurements at the spine and hip with QUS measurements (at the
heel) on three calcaneal ultrasound devices (Hologic Sahara, Hologic
UBA575+ and the Osteometer DTUone). The two groups of women studied were (i)
420 healthy women aged 20-79 years with no known risk factors for
osteoporosis: (ii) 97 postmenopausal women with vertebral fractures)

2k. Using a CUBA
Clinical II device, a BUA threshold of 60 dB/MHz was the most cost-effective
threshold level as a DXA pre-screen. At this threshold, BUA had a
sensitivity of 93% and a specificity of 84% in identifying those subjects
who were subsequently identified as having osteoporosis. Based on local
costs of £45 for DXA and £15 for QUS, QUS assessment does not appear
cost-effective as a pre-screen for DXA, even in a high risk group of women
with low trauma Colles fracture. A QUS pre-screen would only be
cost-effective if the scan could be performed at a substantially lower
costi.

2l. An
evaluation of the Osteoporosis Risk Assessment Instrument (ORAI), a
simple algorithm based on age, weight and current estrogen use, showed
that the tool had a sensitivity of 93.3% (95%CI 86.3-97.0%)
and a specificity of 46.4% (95%CI 41.0-51.8%) for
selecting women with low bone mineral density. The sensitivity for
selecting women with osteoporosis was 94.4% (95%CI
83.7-98.6%)i.

Both the ORAI and SCORE (Simple Calculated Osteoporosis Risk Estimation)
decision rules are better that the National Osteoporosis Foundation
guidelines at targeting BMD testing in high-risk patientsii.

Another assessment tool, based on the results of the Study of Osteoporotic
Fractures (SOF), has recently been published  the FRACTURE Indexiii.
In the model including BMD assessment, dichotomization of the Index at a
cutpoint of 6/15 resulted in a sensitivity of 78.6% and a specificity of
61.7%iii. These results were validated with data for older
women from the EPIDOS Studyiv.(Health gain notation  2 "likely
to be beneficial")

i. Cadarette SM,
Jaglal SB, Kreiger N, McIsaac WJ, Darlington GA, Tu JV. Development and
validation of the Osteoporosis Risk Assessment Instrument to facilitate
selection of women for bone densitometry. Canadian Medical Association
Journal 2000; 162(9): 1289-1294(Type IV evidence 
observational study of 1376 cognitively normal women aged 45 years or more
who had undergone x-ray absorptiometry testing for the Canadian
Multicentre Osteoporosis Study. 926 were allocated to the development of
the tool and 450 to its validation)

2m. Serum C-telopeptide of type I collagen (CTX)
sampled under controlled conditions significantly predicts the
subsequent risk of hip fracture in ambulatory elderly women, with the same
magnitude as urinary markers of resorption. When restricted to samples
taken in the early afternoon, serum CTX was significantly predictive with
a relative hazard of 1.86 (95% CI 1.01-3.76) for
values above the premenopausal range (mean + 2SD)i.

2n. A
survey of General Practitioner (GP) activity in the UK suggested
that GPs are increasingly pro-active in their management of osteoporosis.
Awareness of the clinical factors that predispose individuals to
osteoporosis was reasonably high, but in may cases active management did
not occur until after a patient had had a fracture. One third of GPs were
not satisfied with their access to DXA scans. Prescribing of therapeutic
agents to reduce bone loss appeared to be increasing and a proportion of
GPs were actively implementing guideline recommendations (ranging from 2%
for the Royal College of Physicians guidelines (which had only just been
published) to 29% for local guidelines). However, there was considerable
variation in prescribing patterns and use of diagnostic facilitiesi.Caveat: The
generalisability of these results is seriously weakened by the very low
response rate (20%) and lack of analysis of non-responders.

i. Rowe R. The
management of osteoporosis in general practice: Results of a National
Survey. Osteoporosis Review 1999; 7: 1-3(Type IV evidence  telephone
interview survey of data from 200 GPs who agreed to participate, a 20%
response rate from a random sample of 1009 GPs, stratified by age and
geographical location. GPs were contacted between April and May 1999)